POS0054 DYSFUNCTION OF REGULATORY B CELLS IN GIANT CELL ARTERITIS (GCA)
Authors: M. Stöcker, U. Kiltz, J. Braun, B. Wilde
Journal: Annals of the Rheumatic Diseases (2022)

Background The pathophysiology of GCA is not clearly understood, but most research has pointed towards a major role of T cells with proinflammatory Th1 und Th17 cells as dominant drivers of disease. The role of B cells in the pathogenesis of GCA has not been much studied to date. Objectives To study the role of proinflammatory T cell mediators and anti-inflammatory regulatory B cells (Bregs) as their counterpart in patients with GCA compared to healthy controls (HC). Methods GCA Patients and HC were recruited prospectively and included after informed consent. Peripheral blood mononuclear cells were freshly isolated from whole blood and included into 3 experimental setups, using flow cytometry and fluorescent antibodies: (i) pro-inflammatory T cell mediators (IL-2, GMCSF, IL-17a, IFN-y), (ii) granzyme B production of Bregs after stimulation with different agents (anti-human IgG + IgM, IL-21, anti-CD40L) and (iii) the IL-10 production of Bregs were measured. Disease activity was defined as unequivocal evidence of cranial symptoms of GCA and/or increased concentrations of C-reactive protein and/or halo-sign, leading to a change in therapy according to the treating rheumatologist. Statistical comparisons between groups were performed by the Mann-Whitney-U-Test and Spearman’s rank correlation. Results A total of 47 GCA patients (14 with active disease and 33 in remission) and 49 HC were included (Table 1). CD4 + T cells of GCA patients with active disease produced less IFN-y than HC (p=0.016, Figure 1a). There was also a trend towards lower expression of IL-2 (p=0.18), GMCSF (p=0.1) and IL-17a (p=0.18) by CD4 + T cells from GCA patients compared to HC. Bregs of GCA patients produced lower amounts of granzyme B after stimulation with anti-human IgG and IgM compared to HC, and this was similar in active patients (p=0.04, Figure 1b) and in quiescent patients (p=0.021, Figure 1b). With other stimuli, including IL-21 and anti-CD40L, there was also a trend towards a lower expression. The IL-10 production of Bregs did not show substantial differences between groups. Importantly, the dose of glucocorticoids did not influence cytokine production of T-cells or B-cells. Table 1. Demographics Variables GCA Patients (n=47) Healthy Controls (n=49) Age, years 71 (54-83 ) 65 (45-86 ) Sex, n (%) 31 female (65.9) 40 female (81.6) Disease activity 14 active disease NA (9 first diagnosis, 5 relapse) 33 in remission Therapy Prednisolone: n= 29 none Methotrexat: n=23 Tocilizumab: n=13 Dosage of prednisolone None: n=18 1-7,5 mg/d: n=15 &gt; 7,5 mg/d: n=14 Figure 1. 1a: Interferon gamma expression of CD4+ T-Cells / 1b: Granzyme B expression of Breg after anti-human IgG + IgM stimulation Conclusion The in vitro cytokine production of proinflammatory CD4 + T cells and anti-inflammatory Bregs after stimulation, especially regarding granzyme B production, showed some differences between patients and HC. A lower granzyme B production was found in patients with active disease indicating a lack of Breg–mediated suppressive capacity towards pro-inflammatory T cells. This finding may play a role in the pathogenesis of GCA. References - Disclosure of Interests Marian Stöcker: None declared, Uta Kiltz Speakers bureau: Abbvie, Fresenius, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Amgen, Biogen, Chugai, Eli Lilly, Fresenius, Grünenthal, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Grant/research support from: AbbVie, Amgen, Biogen, Fresenius, GSK, Hexal, Novartis, Pfizer, Juergen Braun Speakers bureau: Abbvie, Amgen, Biogen, BMS, Boehringer, Celltrion, Chugai, Fresenius, Hexal, Janssen, Lilly, Medac, MSD, Mylan, Mundipharma, Novartis, Pfizer, UCB, Paid instructor for: Abbvie, Amgen, Biogen, BMS, Boehringer, Celltrion, Chugai, Fresenius, Hexal, Janssen, Lilly, Medac, MSD, Mylan, Mundipharma, Novartis, Pfizer, UCB, Consultant of: Abbvie, Amgen, Biogen, BMS, Boehringer, Celltrion, Chugai, Fresenius, Hexal, Janssen, Lilly, Medac, MSD, Mylan, Mundipharma, Novartis, Pfizer, UCB, Grant/research support from: Abbvie, Amgen, Biogen, BMS, Boehringer, Celltrion, Chugai, Fresenius, Hexal, Janssen, Lilly, Medac, MSD, Mylan, Mundipharma, Novartis, Pfizer, UCB, Benjamin Wilde Consultant of: Alexion, Chiesi, Hexal, Otsuka, Pfizer, TEVA, Sanofi, Wyeth